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Mice carrying a conditional Serca2(flox) allele for the generation of Ca(2+) handling-deficient mouse models

Kristin B Andersson1, Alexandra V Finsen, Cecilie Sjåland

  • 1Institute for Experimental Medical Research, Oslo University Hospital Ullevaal, Norway. k.b.andersson@medisin.uio.no

Cell Calcium
|August 21, 2009
PubMed

Insights

A new conditional Serca2(flox) mouse model allows organ-specific gene disruption. This tool enables studying SERCA2 function in various tissues and developmental stages, overcoming early embryonic lethality.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Physiology

Background:

  • Sarco(endo)plasmic reticulum calcium ATPases (SERCA) are crucial for calcium transport.
  • Serca2 is the most prevalent SERCA gene, but its null mutants cause early embryonic lethality, hindering research.
  • Previous studies lacked models to investigate Serca2 function in specific organs or at different developmental stages.

Purpose of the Study:

  • To generate a conditional Serca2(flox) mouse model for inducible and organ-specific gene disruption.
  • To overcome the limitations of Serca2(null) mouse lethality.
  • To enable in vivo studies of SERCA2 function in various physiological contexts.

Main Methods:

  • Generation of mice carrying a conditional Serca2(flox) allele.
  • Mating Serca2(flox) mice with Cre-driver lines (MLC-2v(wt/Cre) and alphaMHC-Cre).
  • Analysis of SERCA2 protein expression and embryonic development following gene disruption.

Main Results:

  • The Serca2(flox) model successfully enabled organ-specific and inducible disruption of Serca2.
  • Heterozygous disruption reduced SERCA2a/b in heart and slow skeletal muscle.
  • Homozygous cardiac Serca2 disruption allowed embryonic development up to E10.5, maintaining yolk sac circulation.

Conclusions:

  • The Serca2(flox) mouse is the first conditional knockout model for the SERCA family.
  • This model provides a powerful tool to investigate the physiological roles of SERCA2 in vivo.
  • It facilitates research into SERCA2 function during both embryonic development and in adult organ physiology.

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